This is a study of ADI-PEG 20 (pegylated arginine deiminase), an arginine degrading enzyme versus placebo in patients with malignant pleural mesothelioma with low argininosuccinate synthetase 1 expression. Malignant pleural mesothelioma have been found to require arginine, an amino acid. Thus the hypothesis is that by restricting arginine with ADI-PEG 20, the malignant pleural mesothelioma cells will starve and die.

The purpose of this study is to evaluate the safety of MGD009 when given to patients with B7-H3-expressing tumors. The study will also evaluate what is the highest dose of MGD009 that can be given safely. Assessments will be done to see how the drug acts in the body (pharmacokinetics (PK), pharmacodynamics (PD) and to evaluate potential anti-tumor activity of MGD009.

The purpose of this study is to test the effectiveness and tolerability of the combination of Nivolumab and Ipilimumab compared to Pemetrexed and Cisplatin or Carboplatin in patients with unresectable pleural mesothelioma.

Many tumor cells, in contrast to normal cells, have been shown to require the amino acid glutamine to produce energy for growth and survival. To exploit the dependence of tumors on glutamine, CB-839, a potent and selective inhibitor of the first enzyme in glutamine utilization, glutaminase, will be tested in this Phase 1 study in patients with solid tumors. This study is an open-label Phase 1 evaluation of CB-839 in patients with advanced solid tumors. The study will be conducted in 2 parts. Part 1 is a dose escalation study enrolling patients with locally-advanced, metastatic and/or refractory solid tumors to receive CB-839 capsules orally twice or three times daily. In Part 2, patients with each of the following diseases will be enrolled: A) Triple-Negative Breast Cancer, B) Non-Small Cell Lung Cancer (adenocarcinoma), C) Renal Cell Cancer, D) Mesothelioma, E) Fumarate hydratase (FH)-deficient tumors, F) Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST), G) SDH-deficient non-GIST tumors, H) tumors harboring mutations in isocitrate dehydrogenase-1 (IDH1) or IDH2, and I) cMyc mutation tumors. As an extension of Parts 1 & 2, patients will be treated with CB-839 in combination with standard chemotherapy. Combination groups include: Pac-CB, CBE, CB-Erl, CBD, and CB-Cabo. Pac-CB: patients with locally-advanced or metastatic TNBC will be treated with paclitaxel and CB-839. CBE: patients with advanced clear cell RCC or papillary RCC will be treated with everolimus in combination with CB-839. CB-Erl: patients with advanced NSCLC lacking the T790M EGFR mutation will be treated with erlotinib and CB-839. CBD: patients with NSCLC harboring KRAS mutation will be treated with docetaxel and CB-839. CB-Cabo: patients with histologically confirmed diagnosis of locally-advanced, inoperable or metastatic RCC treated with cabozantinib in combination with CB-839. All patients will be assessed for safety, pharmacokinetics (plasma concentration of drug), pharmacodynamics (inhibition of glutaminase), biomarkers (biochemical markers that may predict responsiveness in later studies), and tumor response.

This is a phase II/III confirmatory study designed to evaluate the safety and efficacy of nintedanib (BIBF 1120) in combination + (pemetrexed / cisplatin) followed by nintedanib (BIBF 1120) versus placebo + pemetrexed / cisplatin followed by placebo for the treatment of patients with unresectable malignant pleural mesothelioma.

RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This randomized phase II trial is studying how well pemetrexed disodium or observation works in treating patients with malignant pleural mesothelioma without progressive disease after first-line chemotherapy.

This is a Phase 2b, randomized, double-blind, parallel-group study. Subjects with unresectable pleural or peritoneal malignant mesothelioma will be randomized in a 2:1 ratio to receive either tremelimumab or placebo. Approximately 564 subjects will be enrolled at study centers in multiple countries. The study consists of a screening period, a treatment period, a 90-day follow-up period for safety, and a long-term survival follow-up period.

This clinical trial will evaluate the safety and immune response of the sequential administration cancer vaccine CRS-207 (with or without cyclophosphamide) followed by standard of care chemotherapy (pemetrexed and cisplatin). CRS-207 is a weakened (attenuated) form of Listeria monocytogenes that has been genetically-modified to reduce its capacity to cause disease, while maintaining its ability to stimulate potent immune responses. CRS-207 has been engineered to elicit an immune response against the tumor-associated antigen mesothelin, which has been shown to be present at higher levels on certain tumor cells (such as mesothelioma) than on normal cells. Pemetrexed and cisplatin are the standard chemotherapy regimen to treat malignant pleural mesothelioma. This trial will evaluate whether giving CRS-207 cancer vaccine with chemotherapy will induce anti-tumor immune responses and/or objective tumor response.

This is a Phase 2, multicenter, open-label, 2-part, single-arm, 2-stage study of tazemetostat 800 mg two times a day (BID) administered orally. Screening of subjects to determine eligibility for the study will be performed within 21 days of the first planned dose of tazemetostat. In Part 1, 12 subjects with relapsed or refractory malignant mesothelioma regardless of BAP1 status will be treated and undergo pharmacokinetics (PK) blood sample collection after a single tazemetostat 800 mg. Part 2 will include subjects with BAP1-deficient relapsed or refractory malignant mesothelioma. Treatment with tazemetostat will continue until disease progression, unacceptable toxicity or withdrawal of consent, or termination of the study. Response assessment will be evaluated after 6 weeks of treatment and then every 12 weeks thereafter while on study.